Using a murine model of acquired immunodeficiency (MAIDS) induced by LP- BM5 retroviruses, we explored whether the presence of retrovirus resistant cells, at the time of infection, would alter the induction and progression of retroviral disease in animals harboring susceptible cellular populations. Allophenic chimeras in which one parent strain was susceptible and the other parent strain resistant to LP-BM5 retroviruses were constructed. Lymphoid chimerism of individual animals was assessed by flow cytometric techniques and the animals subsequently inoculated with the retroviral mix. The animals were assessed for time to lymphadenopathy, time to death, changes in flow cytometric parameters, and for recovery of retroviral species. These studies revealed that the presence of substantial, but less than predominant numbers of resistant cells afforded no protection against disease, with the animals developing lymphadenopathy and dying in the same time frame as fully susceptible control mice and with comparable recovery of retroviral species. However, in animals in which the predominant lymphoid population was of the resistant genotype, the animals failed to develop disease, and little or no retrovirus was recovered. Thus, it is apparent that there is a critical balance between susceptible and resistant lymphoid cells that determines whether the animals succumb to disease, or achieve long term resistance. Additional studies have been planned to elucidate the basis of the failure of suboptimal numbers of resistant cells to confer benefit and to further identify the critical resistant cellular populations responsible for conferring protection against disease.